Synthesis Of The Nucleus MAP And MPP Of Carbapenem Antibiotics’s Key Intermediates

Carbapenem antibiotics with a special β-lactam structure developed in the1970s. Such antibiotics are characterized by broad antibacterial spectrum, strong antimicrobial activity, most clinically stability to β-lactamases and low toxicity et al.. So carbapenems has become a highly effective antimicrobial drug for treatment in serious nosocomial infection. MAP is a carbapenem nucleus that commonly used in the industry currently. But as the protecting groups of the carboxyl of MAP, p-nitro benzyl, which has a negative impact on people. We proposed the construction of MPP from the field of safety, which means allyl instead of p-nitro benzyl with neurotoxicity.The first research is the synthesis process of carbapenem nucleus MAP was studied. Use4-AA as the materials, synthesis the nucleus MAP with five steps of reaction. Influence of reaction conditions, such as:the ratio of raw materials and catalyst et al. on the yield of the target product were studied in detailed. A stable synthesis of nucleus MAP was achieved and the overall yield of the target product was reached to37.7%by optimizing the reaction route.The second research is the synthesis process of nucleus MPP was studied. Use4-AA as the materials similarly, synthesis the nucleus MPP with four steps of reaction. The reaction temperature and the replace of expensive reagents et al. influencing on the reaction results were studied in detailed, and the reaction mechanism was studies in a certain degree.Finally, the total yield of the synthesized target product was54.3%. The synthetic routes of MAP and MPP are related to the Refromatsky reaction and Dickmann condensation reaction.The last research:V2O5/5A catalyst (characterized by X-ray diffraction, N2adsorption/desorption and scanning electron microscope) was used in the oxidation of4-nitrotoluene to4-nitrobenzyl alcohol with H2O2as oxidant in acetic anhydride. Normal to excellent conversion and selectivity were obtained under given conditions.4-nitrobenzyl alcohol was synthesized under simplified operation and green conditions. No V2O5was detected by ICP in the reaction mother liquid, and the recycle test proved the catalyst was stable.